New therapeutic targets for mucosal melanoma identified

View:137 Time:2017-03-20

Melanoma is a rare but aggressive form of skin cancer: it accounts for only 2% of all skin cancers but causes most deaths from skin cancer. Most cases of melanoma result from too much exposure to ultraviolet radiation whereas some cases arise spontaneously from mucosal tissues. For patients with sun-associated melanomas, targeted therapies and immunotherapies are usually very effective. However, for patients with the mucosal form of the disease, these therapies fail to work.

Now a study appearing in the journal Melanoma Research provides an explanation for this and may lead to new treatments for patients with mucosal melanoma. The study, led William Robinson from the University of Colorado Cancer Center, shows that co-mutation of NF1 and KIT, and certain mutations in SF3B1 may be potential new therapeutic targets for mucosal melanoma.

The researchers performed whole-exome sequencing on 135 samples of sun-associated melanoma and 19 samples of mucosal melanoma. Results showed that mutations in the gene BRAF that are common in advanced melanoma were not present in mucosal melanoma. This finding may explain why BRAF-targeted therapies such as vemurafenib are ineffective against mucosal melanoma.

Additionally, they found that 32% of mucosal melanomas had co-mutation in the genes KIT and NF1, and 37% had mutations in the gene SF3B1. Further investigation showed that the mutations in SF3B1 resulted in alternative splicing in multiple genes.

SF3B1 encodes subunit 1 of the splicing factor 3b protein complex, which is a critical component of the splicing machinery. Previous studies have identified mutations in SF3B1 in several different human diseases, including breast cancer, myelodysplastic syndromes, and chronic lymphocytic leukemia.

This study is the first to demonstrate the role of SF3B1 in mucosal melanoma. Moreover, this study is the largest cohort of mucosal melanomas reported with whole-exome sequencing. In the future research, the team will study exactly how SF3B1 mutations affect splicing of genes and tumor progression in mucosal melanoma.